1. Field of the Invention
The present invention relates to novel quaternary ammoniocephalosporins with hydroxylated alicyclic or aliphatic amines of the general formula (I) ##STR2## as useful antibacterial agents and the preparation method thereof. In the formula(I), Q.dbd.CH or N, P.dbd. hydroxylated amine or hydroxylated heterocyclylamines including N-methyl-bis(2-hydroxyethyl)amine, rac-3,4-trans-dihydroxy-1-methylpyrrolidine, (3S, 4S)-3,4-dihydroxy-1-methylpyrrolidine, (3R,4R)-3,4-dihydroxy-1-methylpyrrolidine, meso-3,4-dihydorcy-1-methylpyrrolidine, (2S, 4R)-4-hydroxy-1-methyl-2-pyrrolidinemethanol 3,4-cis-dihydroxy-1-methylpiperidine, 3,4-trans-dihydroxy-1-methylpiperidine, or tropine.
2. Description of the Prior Art
Belgium Pat. No. 876,538 describes the preparation of pyridiniomethyl cephalosporin (ceftazidime), which show broad and potent antibacterial activities. However, it is less active aganist Staphylococci and Enterobacter cloacae P99. Thereafter many quaternary ammoniomethyl cephalosporin derivatives such as cefpirome (Drugs of the Future, 13, 369-371 (1988)) and cefepime (Ger. Pat. No.3,307,550) were developed. Cefpirome is prepared by the reaction of cefotaxime with 2,3-cyclopentenopyridine in the presence of N-methyl-N-(trimethylsilyl)trifluoroactamide or trmethylsilyl iodide. Cefepime is a aminothizolyl cephalosporin derivative having a aliphatic ammonium group at C-3 position and prepared from 7-ACA and 1-methylpyrrolidine. The detailed synthesis of cefepime is described in Journal of Antibiotics, 1986, 39(8), 1092-1107. Cefpirome and cefepime exhibit improved anti-staphylococcal activity while retaining high anti-pseudomonal activity.